crossing96/oncoscreening huggingface dataset:
Efficiency of study designs in diagnostic randomized clinical trials.	From the patients' management perspective, a good diagnostic test should contribute to both reflecting the true disease status and improving clinical outcomes. The diagnostic randomized clinical trial is designed to combine both diagnostic tests and therapeutic interventions. Evaluation of diagnostic tests is carried out with therapeutic outcomes as the primary endpoint rather than test accuracy. We lay out the probability framework for evaluating such trials. We compare two commonly referred designs-the two-arm design and the paired design-in a formal statistical hypothesis testing setup and identify the causal connection between the two tests. The paired design is shown to be more efficient than the two-arm design. The efficiency gains vary depending on the discordant rates of test results. We derive sample size formulas for both binary and continuous endpoints. We derive estimation of important quantities under the paired design and also conduct simulation studies to verify the theoretical results. We illustrate the method with an example of designing a randomized study on preoperative staging of bladder cancer.	bladder
Assessing the invasive potential of bladder cancer: development and validation of a new preclinical assay.	PURPOSE: We developed and validated an electrophysiological method for standardized preclinical assessment of the invasive potential of urothelial carcinoma of the bladder. MATERIALS AND METHODS: Human UMUC-3, RT-112, HT-1197 and T24/83 bladder urothelial carcinoma cells, and UROtsa benign urothelial cells were co-cultivated with high resistance MDCK-C7 cells seeded below a 0.4 μm pore membrane of an insert to avoid physical contact and cellular migration. Transepithelial electrical resistance in Ω cm(2) across the MDCK-C7 monolayer was measured longitudinally. Invasive potential coefficients were calculated based on the secretion of proteolytic factors by invading cells. RESULTS: Consistent transepithelial electrical resistance breakdown patterns were reproduced in 14 or more independent samples of each cell line. Coefficients of invasive potential were significantly higher in bladder urothelial carcinoma than UROtsa cells, including a mean ± SD of 1.5 ± 0.32 vs 9.9 ± 4.97 in UMUC-3, 12.5 ± 6.61 in T24/83, 20.5 ± 4.24 in RT-112 and 21.0 ± 5.15 in HT-1197 cells (p <0.001). No correlation was found between the secretion patterns of matrix metalloproteinase-1, 2 and 9, and invasive potential. Stimulation of UROtsa cells with recombinant human epidermal growth factor up-regulated matrix metalloproteinase-9 secretion and significantly increased invasive potential a mean of 1.3 ± 0.22 vs 14.6 ± 3.28 after stimulation with 10 ng/ml epidermal growth factor (p <0.001). CONCLUSIONS: We developed a highly sensitive translational tool to study the initial process of metastatic spread of urothelial carcinoma of the bladder. The presented electrophysiological invasion assay enables reliable quantification of the invasive potential of bladder urothelial carcinoma cells before physical transmigration. It can be used to identify key molecules for bladder urothelial carcinoma invasion and develop new therapeutic strategies.	bladder
Diagnosis of bladder cancer recurrence based on urinary levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 hypermethylation.	BACKGROUND: Non muscle invasive bladder cancer (NMIBC) has the highest recurrence rate of any malignancy and as many as 70% of patients experience relapse. Aberrant DNA methylation is present in all bladder tumors and can be detected in urine specimens. Previous studies have identified DNA methylation markers that showed significant diagnostic value. We evaluated the significance of the biomarkers for early detection of tumor recurrence in urine. METHODOLOGY/PRINCIPAL FINDINGS: The methylation levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 in urine specimens were measured by real-time PCR (MethyLight). We analyzed 390 urine sediments from 184 patients diagnosed with NMIBC. Urine from 35 age-matched control individuals was used to determine the methylation baseline levels. Recurrence was diagnosed by cystoscopy and verified by histology. Initially, we compared urine from bladder cancer patients and healthy individuals and detected significant hypermethylation of all six markers (P<0.0001) achieving sensitivity in the range 82%-89% and specificity in the range 94%-100%. Following, we validated the urinary hypermethylation for use in recurrence surveillance and found sensitivities of 88-94% and specificities of 43-67%. EOMES, POU4F2, VIM and ZNF154 were more frequently methylated in urine from patients with higher grade tumors (P ≤ 0.08). Univariate Cox regression analysis showed that five markers were significantly associated with disease recurrence; HOXA9 (HR=7.8, P=0.006), POU4F2 (HR=8.5, P=0.001), TWIST1 (HR=12.0, P=0.015), VIM (HR=8.0, P=0.001), and ZNF154 (HR=13.9, P<0.001). Interestingly, for one group of patients (n=15) we found that hypermethylation was consistently present in the urine samples despite the lack of tumor recurrences, indicating the presence of a field defect. CONCLUSION/SIGNIFICANCE: Methylation levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 in urine specimens are promising diagnostic biomarkers for bladder cancer recurrence surveillance.	bladder
Primary adenocarcinoma of the urinary bladder: a single site analysis of 21 cases.	PURPOSE: To investigate whether there is a difference between urachal and non-urachal adenocarcinomas in terms of patient survival and to determine the significant prognostic factors. METHODS: Thirty-four patients with histologically proven adenocarcinoma of the urinary bladder were treated at Huashan hospital between 1999 and 2010. 13 cases were excluded, including 12 patients with metastatic involvement from gastrointestinal or reproductive tracts and one without follow-up data after the initial consultation. Life tables, Kaplan-Meier, Cox regression analysis and log-rank test were used. RESULTS: The difference between patients with urachal adenocarcinoma and patients with non-urachal adenocarcinoma was not statistically significant using the Kaplan-Meier estimates (P = 0.0763). Clinical stage had a significant influence on survival (P = 0.0320, Fig. 2). Patients with surgical resection including partial and radical cystectomy did not have a better prognosis (P = 0.7992, Fig. 3). However, the difference is statistically significant between patients who received partial cystectomy and patients who received radical cystectomy (P = 0.0123, Fig. 4). CONCLUSION: Survival of Patients with adenocarcinoma is correlated with clinical stage. Patients with urachal adenocarcinoma and non-urachal adenocarcinoma may have similar survival outcome. Tumor stage was a highly significant predictor of outcome (P = 0.0320). Surgical resection seems to be more important than chemotherapy in the cases of adenocarcinoma of the urinary bladder. We are in favor of radical cystectomy for all patients.	bladder
Auxotrophic recombinant Mycobacterium bovis BCG overexpressing Ag85B enhances cytotoxicity on superficial bladder cancer cells in vitro.	BCG therapy remains at the forefront of immunotherapy for treating patients with superficial bladder cancer. The high incidence of local side effects and the presence of non-responder diseases have led to efforts to improve the therapy. Hence, we proposed that an auxotrophic recombinant BCG strain overexpressing Ag85B (BCG ∆leuD/Ag85B), could enhance the cytotoxicity to the human bladder carcinoma cell line 5637. The rBCG was generated using an expression plasmid encoding the mycobacterial antigen Ag85B to transform a BCG ∆leuD strain. The inhibitory effect of BCG ∆leuD/Ag85B on 5637 cells was determined by the MTT method, morphology observation and a LIVE/DEAD assay. Gene expression profiles for apoptotic, cell cycle-related and oxidative stress-related genes were investigated by qRT-PCR. Bax, bcl-2 and p53 induction by BCG ∆leuD/Ag85B treatment was evaluated by Western blotting. BCG ∆leuD/Ag85B revealed a superior cytotoxicity effect compared to the control strains used in this study. The results showed that the expression level of pro-apoptotic and cell cycle-related genes increased after BCG ∆leuD/Ag85B treatment, whereas the mRNA levels of anti-apoptotic genes decreased. Interestingly, BCG ∆leuD/Ag85B also increased the mRNA level of antioxidant enzymes in the bladder cancer cell line. Bax and p53 proteins levels increased following treatment. In conclusion, these results suggest that treatment with BCG ∆leuD/Ag85B enhances cytotoxicity for superficial bladder cancer cells in vitro. Therefore, rBCG therapy may have potential benefits in the treatment of bladder cancer.	bladder
[Cystectomy in elderly patients: analysis of complications using the Clavien-Dindo classification].	Radical cystectomy (RC) represents the gold standard in the treatment of muscle invasive urothelial cancer of the bladder. Due to improvements in operation techniques and perioperative care it has become a good and safe procedure even in elderly patients. In recent years the Clavien-Dindo classification has been frequently used for complication assessment in urological research. The Charlson comorbidity index without age correction can be used in treatment planning for RC to identify patients at risk.	bladder
Potentially clinically relevant prostate cancer is found more frequently after complete than after partial histopathological processing of radical cystoprostatectomy specimens.	Incidental prostate cancer is often found in cystoprostatectomy specimens. The presence of a clinically significant tumour has an impact on follow-up strategies. In prostatectomy specimen for prostate cancer, whole-mount sections improve diagnostic accuracy. The present study compares detection of incidental prostate cancer in complete to routine processing. We included 295 consecutive patients who underwent radical cystoprostatectomy. Between 01/1995 and 12/2003 (period I), specimens of 129 patients were partially processed, whereas between 01/2004 and 03/2009 (period II), specimens of 166 patients were completely processed. Incidental prostate cancer was detected overall in 91 (30.8 %) patients. Prostate cancer was detected in 24 (18.6 %) patients in period 1 and in 67 (40.4 %) patients in period 2 (p < 0.001). Potentially clinically significant prostate cancer was detected in 12 (9.2 %) and 29 (17.5 %) patients, respectively (p = 0.044). Complete embedding and processing of cystoprostatectomy specimen yield significantly more potentially clinically relevant prostate cancers. The present data suggest that notably in younger men the specimens should be completely processed.	bladder
Risk of radiogenic second cancers following volumetric modulated arc therapy and proton arc therapy for prostate cancer.	Prostate cancer patients who undergo radiotherapy are at an increased risk to develop a radiogenic second cancer. Proton therapy has been shown to reduce the predicted risk of second cancer when compared to intensity modulated radiotherapy. However, it is unknown if this is also true for the rotational therapies proton arc therapy and volumetric modulated arc therapy (VMAT). The objective of this study was to compare the predicted risk of cancer following proton arc therapy and VMAT for prostate cancer. Proton arc therapy and VMAT plans were created for three patients. Various risk models were combined with the dosimetric data (therapeutic and stray dose) to predict the excess relative risk (ERR) of cancer in the bladder and rectum. Ratios of ERR values (RRR) from proton arc therapy and VMAT were calculated. RRR values ranged from 0.74 to 0.99, and all RRR values were shown to be statistically less than 1, except for the value calculated with the linear-non-threshold risk model. We conclude that the predicted risk of cancer in the bladder or rectum following proton arc therapy for prostate cancer is either less than or approximately equal to the risk following VMAT, depending on which risk model is applied.	bladder
Expression of TIP60 (tat-interactive protein) and MRE11 (meiotic recombination 11 homolog) predict treatment-specific outcome of localised invasive bladder cancer.	What's known on the subject? and What does the study add? Several studies have shown that defects in DNA-damage response are associated with good survival after chemotherapy and radiotherapy. Furthermore, loss of cell cycle regulators may be prognostic indicators of poor survival after cystectomy. However, the potential clinical impact of previous findings is hampered by insufficient validation of significant results in suitable cystectomy and radiotherapy cohorts. Here we use a large cohort of patients receiving radiotherapy to successfully validate the importance of MRE11 as a predictive marker of disease-specific survival (DSS). Furthermore, using two independent patient cohorts we show for the first time that TIP60 is a predictive marker of DSS after cystectomy. We show that combined use of TIP60 and MRE11 may hold the potential to guide treatment decisions. OBJECTIVE: • To determine the association between the proteins: tat-interactive protein 60 kDa (TIP60), p16, meiotic recombination 11 homolog (MRE11), phosphorylated ataxia telangiectasia mutated (ATM), retinoblastoma protein (Rb), Ki67, and p53 and clinical outcome in invasive lymph node-negative bladder cancer. PATIENTS AND METHODS: • Protein expression was measured by immunohistochemistry in cancer specimens from two independent cohorts of patients with bladder cancer treated with cystectomy (162 patients and 273) and one cohort of patients receiving radiotherapy (148). • Disease-specific survival (DSS) was used as the outcome measure, and patients with no disease-specific death were followed for a minimum of 36 months. RESULTS: • TIP60 was significantly correlated with DSS in both cystectomy cohorts (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.26-0.68, P < 0.001 and HR 0.45, 95% CI 0.28-0.72, P = 0.001). • MRE11 was significantly correlated with DSS in the cohort receiving radiotherapy (HR 0.64, 95% CI 0.47-0.86, P = 0.005). • P16 was significantly correlated with DSS in all three cohorts (HR 0.46, 95% CI 0.30-0.75, P = 0.032; HR 0.60, 95% CI 0.37-0.97, P = 0.032; HR 0.52, 95% CI 0.28-0.96, P = 0.001). • Rb was significantly correlated with DSS in one cystectomy cohort (HR 1.71, 95% CI 1.13-2.75, P = 0.017). • Ki67, p53, and pATM were not significantly correlated with DSS in any of the cohorts. CONCLUSIONS: • TIP60 protein expression was a predictive marker for DSS after cystectomy in two independent cohorts. This novel marker was the strongest predictive factor in multivariate analysis in patients receiving cystectomy. • MRE11 was shown to be a predictive marker for DSS after radiotherapy. • We have shown that TIP60 and MRE11 hold the potential to guide patients with invasive bladder cancer to either cystectomy or radiotherapy. This study was based on retrospective material and consequently we suggest that these markers should be validated in a prospective study.	bladder
Smoking and survival after radical cystectomy for bladder cancer.	OBJECTIVE: To present our long-term follow-up data to investigate whether cigarette smoking is associated with the prognosis of bladder cancer after radical cystectomy. Despite the close link between cigarette smoking and the development of bladder cancer, little is known about the influence of cigarette smoking on the bladder cancer prognosis after radical cystectomy. MATERIALS AND METHODS: The cigarette smoking status of 602 patients who had undergone radical cystectomy for bladder cancer was determined using questionnaires completed before surgery. The effect of cigarette smoking on recurrence-free survival, cancer-specific survival, and overall survival was determined. RESULTS: Of the 340 patients with a smoking history, 159 were current smokers. The smokers were younger (P = .001) and more likely to be male (P = .001) than were the nonsmokers. The 5-year recurrence-free survival rate of the smokers and nonsmokers was 62.1% and 56.8% (P = .182), the 5-year cancer-specific survival rate was 67.3%, 63.9% (P = .436), and the 5-year overall survival rate was 63.0% and 58.8% (P = .309), respectively. Multivariate analysis revealed that smoking was not an independent predictor of recurrence-free survival or cancer-specific survival. After adjusting for other prognostic variables, cigarette smoking status (non-, ex-, or current smoker), cumulative exposure, and years from smoking cessation were not associated with cancer-specific survival (P = .378, P = .827, and P = .876, respectively). CONCLUSION: The results of the present study found no association between cigarette smoking and the prognosis of bladder cancer after radical cystectomy.	bladder
DNA damage in exfoliated cells and histopathological alterations in the urinary tract of mice exposed to cigarette smoke and treated with chemopreventive agents.	Cigarette smoke (CS) is convincingly carcinogenic in mice when exposure starts at birth. We investigated the induction and modulation of alterations in the kidney and urinary bladder of CS-exposed mice. A total of 484 strain H Swiss mice were either sham-exposed or exposed since birth to mainstream CS (MCS) for 4 months. Dietary agents, including myo-inositol, suberoylanilide hydroxamic acid, bexarotene, pioglitazone and a combination of bexarotene and pioglitazone, were administered after weaning. Comet analyses showed that, after 2 and 4 months, MCS causes DNA damage in exfoliated urothelial cells, which can be prevented by myo-inositol and the peroxisome proliferator-activated receptor-γ ligand pioglitazone. After 7 months, the 17.6% of MCS-exposed male mice exhibited lesions of the urinary tract versus the 6.1% of sham-exposed mice, which emphasizes the role of sex hormones in urinary tract carcinogenesis. Myo-inositol and the RXR-specific retinoid bexarotene did not affect these alterations. The histone deacetylase inhibitor suberoylanilide hydroxamic acid (Vorinostat) increased the incidence of kidney epithelium hyperplasia. Pioglitazone significantly enhanced the incidence of kidney lesions as compared with mice exposed to MCS only, indicating possible adverse effects of this antidiabetic drug, which were lost upon combination with bexarotene according to a combined chemoprevention strategy. RXR is a heterodymeric partner for peroxisome proliferator-activated receptor-γ, thereby modulating the expression of multiple target genes. In conclusion, there is contrast between the ability of pioglitazone to inhibit DNA damage in exfoliated cells and the alterations induced in the urinary tract of MCS-exposed mice, suggesting the occurrence of non-genotoxic mechanisms for this drug.	bladder
Current status of targeted therapy in metastatic transitional cell carcinoma of the bladder.	Urothelial bladder cancer is the second most common genitourinary GU cancer and is among the deadliest and most expensive cancers to treat. The introduction of new regimens improving outcomes of bladder cancer has been slow compared to other GU cancers. This is despite the fact that understanding of the genetic make up of this disease is relatively old. Based on this knowledge, many targets have been identified and therapeutic strategies laid out. This article reviews the literature on the biology of the bladder cancer as it relates to identification of targets. It also provides a review of the data from clinical trials that were designed to test the therapeutic strategies that exploit these targets.	bladder
Innovations in radical cystectomy and pelvic lymph node dissection.	Radical cystectomy with bilateral pelvic lymphadenectomy remains the gold standard in the surgical management of muscle-invasive urothelial carcinoma of the bladder and provides optimal locoregional cancer control in conjunction with perioperative cisplatin-based chemotherapy. Improvements in preoperative staging can aid in the identification of patients who may optimally benefit from neoadjuvant chemotherapy and determine candidacy for orthotopic neobladder reconstruction. Innovations in surgical technique and perioperative care have helped to minimize patient morbidity and preserve long-term urinary and sexual function while maintaining oncologic control. The use of minimally invasive surgical approaches has grown dramatically in urologic surgery over the past decade and the preliminary results of robot-assisted laparoscopic radical cystectomy have been reported recently. Anatomic pelvic and iliac lymphadenectomy is crucial for precise pathologic staging and may improve patient survival by removing micrometastatic disease.	bladder
Management of non-muscle-invasive (superficial) bladder cancer.	Non-muscle-invasive (superficial) bladder cancer (NMIBC) represents 80% of incident cases of bladder cancer, and is characterized by a generally good prognosis, with a tendency to remain localized. Only 10%-20% of cases progress to invasion and/or metastasis. The biggest problem in management is the potential for local recurrence, and this will occur with relatively predictable prognostic determinants. Gene expression and other cell surface determinant are associated with outcome. In most cases, successful management is predicated on careful history taking and physical assessment, meticulous endoscopic assessment, and transurethral resection of bladder tumor tissue where indicated. Histology determines the potential for recurrence. Options of treatment include repeat resection, immunologic therapy via intravesical instillation, and the use of intravescally administered cytotoxic agents, including mitomycin C, doxorubicin, gemcitabine, and selected investigational compounds. Of importance, as some cases have the potential to invade and metastasize, timing of cystectomy for recurrent, high-risk tumors is important to avoid unnecessary morbidity and mortality.	bladder
Radiologic imaging of patients with bladder cancer.	Imaging has an ancillary but important role in the detection, staging, and follow-up of bladder cancer. Computed tomography urography (CTU) has widely replaced intravenous urography (IVU) and is currently the imaging modality most commonly used for the initial evaluation of patients with or suspected of having bladder tumors, as CTU allows a fast and comprehensive evaluation of the urinary tract in a single exam. Magnetic resonance imaging (MRI) affords better soft tissue contrast, which allows for more accurate staging than can be achieved with other imaging modalities; the role of MRI in bladder cancer is expected to grow. Despite myriad technical advances, imaging of the bladder has several limitations and technical challenges. The performance of the common and some promising newer imaging modalities in the evaluation of bladder cancer are discussed.	bladder